%0 Journal Article
%T Applying Neural ODEs to Derive a Mechanism-Based Model for Characterizing Maturation-Related Serum Creatinine Dynamics in Preterm Newborns.
%A Bräm DS
%A Koch G
%A Allegaert K
%A van den Anker J
%A Pfister M
%J J Clin Pharmacol
%V 0
%N 0
%D 2024 May 16
%M 38752504
%F 2.86
%R 10.1002/jcph.2460
%X Serum creatinine in neonates follows complex dynamics due to maturation processes, most pronounced in the first few weeks of life. The development of a mechanism-based model describing complex dynamics requires high expertise in pharmacometric (PMX) modeling and substantial model development time. A recently published machine learning (ML) approach of low-dimensional neural ordinary differential equations (NODEs) is capable of modeling such data from newborns automatically. However, this efficient data-driven approach in itself does not result in a clinically interpretable model. In this work, an approach to deriving an interpretable model with reasonable PMX-type functions is presented. This "translation" was applied to derive a PMX model for serum creatinine in neonates considering maturation processes and covariates. The developed model was compared to a previously published mechanism-based PMX model whereas both models had similar mechanistic structures. The developed model was then utilized to simulate serum creatinine concentrations in the first few weeks of life considering different covariate values for gestational age and birth weight. The reference serum creatinine values derived from these simulations are consistent with observed serum creatinine values and previously published reference values. Thus, the presented NODE-based ML approach to model complex serum creatinine dynamics in newborns and derive interpretable, mathematical-statistical components similar to those in a conventional PMX model demonstrates a novel, viable approach to facilitate the modeling of complex dynamics in clinical settings and pediatric drug development.